Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation?Positive Non?Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study
Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation?Positive Non?Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study
复制标题
DOI：
10.1200/jco.19.00457
复制
发表时间：
2020-02-20
影响因子：
45.3
通讯作者：
Ahn, Myung-Ju
中科院分区：
文献类型：
--
作者：
Yang, James C. H.;Kim, Sang-We;Ahn, Myung-Ju
在这项I期研究（BLOOM）中，奥希替尼，一种第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），在EGFR突变（EGFRm）晚期非肿瘤患者的软脑膜转移（LM）中进行了评估。既往接受EGFR-TKI治疗后疾病进展的小细胞肺癌（NSCLC）。患者和方法细胞学证实的LM患者接受奥希替尼160 mg每日一次。目的是评估确认的客观缓解率（ORR）、缓解持续时间（DoR）、无进展生存期（PFS）、总生存期（OS）、药代动力学（PK）和安全性。其他疗效评价包括CSF细胞学和神经系统检查较基线的变化。研究者根据RECIST 1.1版评估可测量病灶。根据神经肿瘤学LM放射学缓解评估标准，通过神经放射学设盲中心独立审查（BICR）和研究者评估LM。结果41例患者入组。神经放射学BICR评估的LM ORR和DoR分别为62%（95% CI，45%-78%）和15.2个月（95% CI，7.5 - 17.5个月）。总体而言，研究者评估的ORR为41%（95% CI，26%-58%），中位DoR为8.3个月（95% CI，5.6 - 16.5个月）。中位评估者评估的PFS为8.6个月（95% CI，5.4 - 13.7个月），成熟度为78%;中位OS为11.0个月（95% CI，8.0 - 18.0个月），成熟度为68%。40例患者中有11例（28%; 95% CI，15%-44%）证实了CSF肿瘤细胞清除。基线评估异常的21例患者中有12例（57%）神经功能改善。不良事件和PK特征与奥希替尼的既往报告一致。结论奥希替尼在EGFRm NSCLC和LM患者中显示出有意义的CNS治疗疗效和可管理的安全性特征，160 mg每日一次。
PURPOSE In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non?small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy. PATIENTS AND METHODS Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Additional efficacy evaluations included changes from baseline in CSF cytology and neurologic examination. Measurable lesions were assessed by investigator according to RECIST version 1.1. LMs were assessed by neuroradiologic blinded central independent review (BICR) according to Response Assessment in Neuro-Oncology LM radiologic criteria and by investigator. RESULTS Forty-one patients were enrolled. LM ORR and DoR by neuroradiologic BICR were 62% (95% CI, 45% to 78%) and 15.2 months (95% CI, 7.5 to 17.5 months), respectively. Overall, ORR by investigator was 41% (95% CI, 26% to 58%), and median DoR was 8.3 months (95% CI, 5.6 to 16.5 months). Median investigator-assessed PFS was 8.6 months (95% CI, 5.4 to 13.7 months) with 78% maturity; median OS was 11.0 months (95% CI, 8.0 to 18.0 months) with 68% maturity. CSF tumor cell clearance was confirmed in 11 (28%; 95% CI, 15% to 44%) of 40 patients. Neurologic function was improved in 12 (57%) of 21 patients with an abnormal assessment at baseline. The adverse event and PK profiles were consistent with previous reports for osimertinib. CONCLUSION Osimertinib showed meaningful therapeutic efficacy in the CNS and a manageable safety profile at 160 mg once daily in patients with EGFRm NSCLC and LM.